Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of cyclic AMP (cAMP) and its metabolites (5'-AMP and adenosine) as well as the adenyl cyclase, cAMP phosphodiesterase, and 5'-nucleotidase activities were determined in lymphocytes of thymus, spleen, and lymph nodes of control and protein-deficient rats. The values of these parameters, when expressed as per milligran DNA and as per 10-8 cells, but not always when expressed as per milligran protein, were much lower in the thymus as compared with the spleen and the lymph nodes in the control rats. The protein-deficient diet increased the nucleotide concentrations in the thymus and spleen lymphocytes on a per milligram DNA basis except those of thymic cAMP, which did not change. The same diet also increased the activities of the enzymes involved in the cAMP metabolism in thymic, splenic, and lymph node lymphocytes. Such a peculiarity could be related to the reduction of the mitotic activity of lymphocytes caused by protein deficiency since an inverse relationship has been reported between this activity and the synthesis of cAMP. On the other hand, it was noted that purified lymphocyte suspensions contained paradoxically higher amounts per cell of DNA, RNA, and protein in the thymus, spleen, and lymph nodes of protein-deficient rats as compared with those of the control rats. However, when the cell preparations were not purified, only the lymph node cells displayed a strong increase in their DNA content. Prolongation of the S phase of the cell cycle in these lymphocytes is suggested.
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PMID:Cyclic AMP metabolism and nucleic acid content in the lymphocytes of the thymus, spleen, and lymph nodes of protein-deficient rats. 16 50

Male CF-1 mice were treated for 14 days with diets containing haloperidol, thioridazine HCl and 4'-fluoro-4[[4-(p-fluorophenyl)-4-methoxycyclohexyl]-amino]-butyrophenone HCl (U35,777A). At various times during and after neuroleptic treatment, spontaneous and d-amphetamine-stimulated motor activity were measured. Two days after cessation of treatment, the mice displayed enhanced spontaneous and d-amphetamine-stimulated motor activity. This effect was no longer apparent 9 days after neuroleptic intake was terminated. With a quantal test based on the climbing activity induced by apomorphine, it was determined that mice were also supersensitive to apomorphine at 2 days but not 9 days after withdrawal from chronic haloperidol. In an attempt to correlate this supersensitivity to a biochemical parameter related to receptor function, dopamine-stimulated adenyl cyclase activity was assayed in striatal homogenates of mice 2 days after haloperidol withdrawal. No alteration in this parameter was observed. Likewise, the ability of apomorphine to elevate striatal cyclic adenosine monophosphate concentrations in vivo was unaltered by withdrawal from chronic haloperidol. Chronic treatment with neuroleptics results in a brief supersensitivity to dopaminergic agents. This effect does not appear to be accompanied by increases in dopamine-stimulated adenyl cyclase activity in the corpus striatum.
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PMID:Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment. 16 58

Rat epididymal tubules maintained in organ culture for 3 days respond to the addition of androgens to the culture media (testosterone and dihydrotestosterone 1 x 10-minus 5 m and 1 x 10-minus 7 m) with an increased incorporation of amino acids into acid-insoluble material. Significant androgenic stimulation is observed only 24 h after addition of hormone, while an inhibitory effect is found at earlier periods. The stimulation seems to be specifically produced by androgens; it is blocked by cyproterone acetate and is not elicited by oestradiol-17beta or corticosterone. The process appears to involve RNA synthesis since actinomycin D suppresses the stimulatory effect of androgen. Evidence suggests that cAMP production is not a primordial step in the response to androgen since dibutyryl cAMP did not mimick the androgenic effect, theophylline did not potentiate the response and alpha,beta-methylene ATP, which competitively inhibits adenyl cyclase, failed to alter the androgenic effect. Radioactive testosterone and dihydrotestosterone added to the culture media showed a preferential intranuclear localization as well as extensive metabolism. DHT was found to be the principal intranuclear steroid.
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PMID:The influence of androgens on protein synthesis by cultured rat epididymal tubules. 16 37

Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.
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PMID:Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle. 16 62

The relaxing effect of isoproterenol on aortic strips from rats decreases and disappears with increasing age of the animal. In aortas from young rats (1 month) the cAMP level increases after stimulation with isoproterenol (3.6 muM), whereas in old aortas (6 months) the cAMP level was unchanged. Basal and NaF stimulated adenyl cyclase activities are increased in aortas from rats 6 months of age compared with those one month old. The phosphodiesterase activities decrease with increasing age both low (10-7M) and high (10-4M) substrate concentration.
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PMID:Adrenergic beta-receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age. 16 39

Slices of human skin obtained with a keratome were pre-incubated with [3H]adenine to label the ATP pool from which cyclic AMP was subsequently formed. The accumulation of radioactive cyclic AMP was measured as an index of adenyl cyclase activity. The data showed that both the ability to incorporate [3H] into ATP and adenyl cyclase activity were significantly lower in psoriatic plaques than in uninvolved skin of the psoriatic patients, or in normal skin of control subjects. The response of adenyl cyclase to the stimulation of 3.3 muM adrenaline was less than five fold in psoriatic plaques as compared to twelve to thirty-two fold in the uninvolved skin. The response to the stimulation of prostaglandin E2 (5 mug/ml) showed no significant difference between the plaque and normal skin. The adenyl cyclase activity in uninvolved skin of psoriatic patients appeared normal. Propranolol (10 muM) blocked the stimulatory effect of adrenaline but not that of PGE2 in normal skin. These results suggest that the adenyl cyclase system of the skin has different regulatory sites for adrenaline and PGE2 and that the enzyme is defective in the epidermis of the psoriatic plaque, especially at the adrenaline regulatory site.
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PMID:Further studies on adenyl cyclase in psoriasis. 16 99

Human chorionic somatomammotropin extracted and purified from placenta at term was proved to have a lipolytic action in the epididymal fat pad of rats. The following mechanism appears to be involved in the lipolytic action of the hormone; human chorionic somatomammotropin activates adenyl cyclase, thereby increasing the concentration of cyclic AMP in the tissue, which, in turn, activates protein kinase to lead to the activation of hormone sensitive lipase.
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PMID:Lipolytic action of human chorionic somatomammotropin. 16 57

The effect of hypoxia on glycogen content, adenyl cyclase activity, cyclic 3',5'-AMP concentration, lactate: pyruvate ratio and the energy charge potential connected with the pool of adenylates was evaluated in the motor area of the cortex of beagle dogs. At first, controlled hypoxia induces activation of the adenyl cyclase system while subsequently, with PaO2 values lower than 20 mm Hg, a depression of the system is observed simultaneously with a drop of the energy charge potential. When normal oxygenation is resumed, the biochemical parameters examined tend to go back to normal even though it is still necessary to resort to anaerobic mechanisms. The intracarotid perfusion with nicergoline enhances the post-hypoxic recovery of adenyl cyclase activity, even though the ergoline derivative is inactive during the stages of hypoxic suffering of the brain studied in the present work.
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PMID:Effect of hypoxia on the cerebral energy state. 16 98

Isolated adrenal cells were obtained surgically from patients with primary aldosteronism, breast cancer, or Cushing's syndrome. They were prepared by the modification of Sayers method, and incubated at 37 degrees C for 2 hours under 95% O-2-5% CO-2, in the medium of calcium-free Krebs-Ringer bicarbonate buffer containing 0.2% glucose and 0.5% bovine serum albumin, to which various doses of calcium, ACTH, dibutyryl cyclic AMP or cycloheximide were added. Steroid production was measured by the method of Silber et al. In isolated normal adrenocortical cells, 11-OHCS was produced by calcium alone in the absence of ACTH or dibutyryl cyclic AMP, while it was not produced by ACTH alone without calcium. 11-OHCS production by ACTH was decreased in the high concentration of calcium (10.16 mM, 12.70 mM). Cycloheximide partially blocked an increase in 11-OHCS synthesis induced by calcium. These data suggest that adenyl cyclase of human adrenocortical cells may be stimulated by calcium alone, supporting the notion that calcium is a second messenger. The ratio of 11-OHCS production by calcium alone to that by dibutyryl cyclic AMP was higher in adenoma cells than in normal cells. This may account for the character of autonomic steroid production in adrenocortical adenoma cells.
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PMID:[Effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)]. 16

Positive selection procedures for mutants of Salmonella typhimurium lacking cyclic 3', 5'7-adenosine monophosphate (cAMP) phosphodiesterase have been devised. The gene (cpd) coding for this enzyme has been located on the chromosome and shown to be 25% co-transducible with metC using phage P22. The mutants have been used to investigate the role of the enzyme in the control of genes whose expression is known to be dependent on cAMP. Significant alterations in the regulation of some but not others of these genes have been observed in these mutants. Mutants lacking the cAMP phosphodiesterase are more sensitive than their parents to a variety of antibiotics that appear to enter the cell through cAMP-dependent transport systems. They grow faster than the wild type on succinate-ammonia-salts, and glucose-proline-salts media and are inhibited by added cAMP on glucose, citrate, or glycerol-ammonia salts media whereas the wild type is unaffected. Neither the growth of Salmonella typhimurium on glycerol or citrate media nor the level of acid hexose phosphatase in the strain is affected by the loss of cAMP phosphodiesterase. In addition, the mutant strains are extremely sensitive to high levels of cAMP. Loss of the cAMP phosphodiesterase in strains unable to synthesize cAMP (adenyl cyclase negative) reduces by 10-fold the requirement for exogenous cAMP for expression of catabolite-sensitive phenotypes. These results suggest that through its control of cAMP levels in the cell the phosphodiesterase may be involved in the regulation of certain classes of catabolite-sensitive operaons and also in protecting the cell against high levels of cAMP.
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PMID:Cyclic 3', 5'-adenosine monophosphate phosphodiesterase mutants of Salmonella typhimurium. 16 78


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